This proposal outlines a program to develop new synthetic neuraminidase substrates and neuraminic acid derivatives for the purpose of studying neuraminidases and hemagglutinins: 1) We plan to synthesize neuraminidase substrates for use in histochemistry, substrates of this kind should help elucidate the exact localization and the role of neuraminidase in influenza virus infected cells as well as in uninfected cells. 2) Similar synthetic methods will be applied to prepare radioactively labeled substrates which are highly sensitive in detecting neuraminidase activity and substrates which will allow the routine determination of neuraminidases from mammalian, bacterial and viral sources. A prototype of these substrates (2-(3'-methoxyphenyl)-alpha-N-acetyl- neuraminic acid (MPN)) has been prepared for the Research Resources Branch of the NIAID and is currently being distributed among interested scientists. 3) Besides the development of new neuraminidase substrates, we will continue and extend studies to detect mutants of influenza viruses with either high or low neuraminidase content using the chromogenic neuraminidase substrate MPN. 4) Attempts will be made to prepare a neuraminic acid adsorbent specific for neuraminidases and hemagglutinins, and thereby to study the specificity of hemagglutinin from different viruses and to identify inhibitors directed against the neuraminidase and hemagglutinin activity of influenza viruses.